Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer.

BACKGROUND

Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes.

METHODS

Secondary end-points of NEOPAL included progression-free survival (PFS) and invasive-disease free survival (iDFS) in the intent-to-treat population. Exploratory end-points were overall survival (OS) and breast cancer specific survival (BCSS) in the intent-to-treat population, as well as iDFS, OS and BCSS according to the administration of chemotherapy.

RESULTS

Hundred and six patients were randomised. Pathological complete response rates were 3.8% and 5.9%. Twenty-three of the 53 patients in the letrozole-palbociclib arm received postoperative adjuvant chemotherapy. At a median follow-up of 40.4 months [0-56.6], 11 progressions have been observed, of which three were in the letrozole-palbociclib and 8 in the control arm. PFS (HR = 1.01; [95%CI 0.36-2.90], p = 0.98) and iDFS (HR = 0.83; [95%CI 0.31-2.23], p = 0.71) did not differ between both arms. The 40 months PFS rate was 86.7% [95%CI 78.0-96.4] and 89.9% [95%CI 81.8-98.7] in letrozole-palbociclib and control arms, respectively. Outcomes of patients who did not receive chemotherapy were not statistically different from those who received it.

CONCLUSIONS

NEOPAL suggests that a neoadjuvant letrozole-palbociclib strategy may allow sparing chemotherapy in some patients with luminal breast cancer while allowing good long-term outcomes. Larger confirmatory studies are needed.

Informations de copyright

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Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SDe, PC and JL report institutional funding for the present trial from Pfizer and Nanostring technologies. SDe reports institutional consulting fees from AstraZeneca, Besins, Sanofi, Rappta; institutional honoraria from AstraZeneca, Seagen, MSD, Pfizer; institutional investigating fees from Taiho, AstraZeneca, Pfizer, MSD, Novartis, Sanofi, G1 therapeutics, BMS, Pfizer, Roche; and personal support for attending US conference from AstraZeneca and Pfizer. FL reports honoraria from AstraZeneca, EISAI, Lilly, Novartis, P Fabre, Roche; support for attending meetings from AstraZeneca, EISAI, Lilly, Novartis, P Fabre, Pfizer, Roche; participation on IDMC or advisory boards from AstraZeneca, EISAI, Lilly, Pierre Fabre, Roche. JSF reports personal consulting fees from ROCHE, ASTRA ZENECA, NOVARTIS, DAIICHI, LILLY, PFIZER, CLOVIS, GSK, MSD; honoraria from ASTRA ZENECA, NOVARTIS, DAIICHI, LILLY, PFIZER, CLOVIS, MSD, AMGEN; support for attending meetings from ASTRA ZENECA, NOVARTIS, DAIICHI, LILLY, PFIZER, CLOVIS, MSD; participation on IDMC or advisory board from ASTRA ZENECA, NOVARTIS, DAIICHI, LILLY, PFIZER, CLOVIS, MSD, PIERRE FABRE. PEH reports consulting fees from Novartis, Pfizer, Lilly; and support from Mylan, Eisei, Roche, Novartis. VDH reports support for attending meetings from Roche, Novartis Pfizer. CJ reports personal honoraria from Daiichi, AstraZeneca, Pfizer. FD reports consulting fees from Roche, Pfizer, AstraZeneca, Lilly, Novartis, Amgen, Daiichi, Pierre Fabre, Seagen; and support for attending meetings from Roche and Pfizer. PC reports personal consulting fees from Pfizer, Roche, Lilly, Novartis, Daiichi and Seagen, honoraria from Pfizer and Novartis. The others did not report disclosures.